pH响应海藻酸@介孔二氧化硅/阿霉素纳米粒子的制备及应用研究
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摘要
目的:本研究利用静电吸附制备海藻酸包裹介孔二氧化硅纳米(mesoporous silica nanoparticles,MSN)药物传递体系,考察其在肿瘤细胞中pH响应释放性能。方法:以溶胶-凝胶法制备了介孔二氧化硅纳米粒子,经氨基化修饰后载入盐酸阿霉素(doxorubicin,DOX),得到载药纳米粒子。载药纳米粒子表面的氨基能通过静电作用吸附海藻酸(alginate,SA)。海藻酸的吸附包裹能对介孔进行封堵,抑制药物的释放,在肿瘤组织偏酸性环境中,海藻酸与氨基的静电作用减弱,从纳米粒子表面脱落,药物能够顺利释放。结果:透射电镜结果显示海藻酸成功包覆在介孔二氧化硅纳米粒子表面。体外药物释放实验结果表明海藻酸的包覆能有效抑制药物在pH 7. 4环境下释放。体外细胞抑制实验结果显示海藻酸的包覆能明显提升正常细胞293T的存活率,对肿瘤细胞HeLa细胞的影响较小。结论:海藻酸包覆的介孔二氧化硅纳米粒子能在肿瘤细胞中进行pH响应释放。
Objective: In this study,a drug delivery system based on mesoporous silica nanoparticles( MSN) capped by alginate was fabricated via electrostatic interaction to investigate its performance of p H-responsive drug release in tumor cells. Methods: MSN were prepared by sol-gel method. Doxorubicin( DOX) was loaded into the nanoparticles which were modified by NH2-group. The amino groups on the surface of the drug-carrying nanoparticles could absorb alginate( SA) via electrostatic interaction. The adsorption coating of alginate could block the mesoporous pores and inhibit the release of drugs. In the acidic environment of tumor tissue,the electrostatic interaction between alginate and amino group was weakened,and the nanoparticles were detached from the surface,so that the drug could be released smoothly. Results: The TEM images show that MSN/DOX were successfully coated by alginate. The result of in vitro drug release shows that alginate coating can effectively inhibit the drug release from pore of SA@ MSN/DOX at pH 7. 4. Through the cell growth inhibition result,it can be seen that cell viability of293 T cells treated by SA@ MSN/DOX is obviously higher than that of MSN/DOX,and there is no significant difference in HeLa cells. Conclusions: Alginate-coated mesoporous silica nanoparticles can performance of pH-responsive drug release in tumor cells.
Objective: In this study,a drug delivery system based on mesoporous silica nanoparticles( MSN) capped by alginate was fabricated via electrostatic interaction to investigate its performance of p H-responsive drug release in tumor cells. Methods: MSN were prepared by sol-gel method. Doxorubicin( DOX) was loaded into the nanoparticles which were modified by NH2-group. The amino groups on the surface of the drug-carrying nanoparticles could absorb alginate( SA) via electrostatic interaction. The adsorption coating of alginate could block the mesoporous pores and inhibit the release of drugs. In the acidic environment of tumor tissue,the electrostatic interaction between alginate and amino group was weakened,and the nanoparticles were detached from the surface,so that the drug could be released smoothly. Results: The TEM images show that MSN/DOX were successfully coated by alginate. The result of in vitro drug release shows that alginate coating can effectively inhibit the drug release from pore of SA@ MSN/DOX at pH 7. 4. Through the cell growth inhibition result,it can be seen that cell viability of293 T cells treated by SA@ MSN/DOX is obviously higher than that of MSN/DOX,and there is no significant difference in HeLa cells. Conclusions: Alginate-coated mesoporous silica nanoparticles can performance of pH-responsive drug release in tumor cells.
引文
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[15] MURDZHEVA D,PETKOVA N,TODOROVA M,et al. Microwave-assisted synthesis of methyl esters of alginic acids as potential drug carrier[J]. J Pharmaceut Biomed,2016,8(10):1361-1368.
[16]周毅,李旭丰,谭璐,等.海藻酸栓塞微球可视化及作为药物载体研究进展[J].中国新药杂志,2017,26(9):1024-1028.
[17] MANCHUN S,DASS CR,SRIAMORNSAK P. Targeted therapy for cancer using pH-responsive nanocarrier systems[J]. Life Sci,2007,80(5):381-387.
[18] HU C,HUANG P,ZHENG Z,et al. A facile strategy to prepare an enzyme-responsive mussel mimetic coating for drug delivery based on mesoporous silica nanoparticles[J]. Langmuir,2017,33(22):5511-5518.
[19]许金霞,唐建斌,赵鲁杭,等.肿瘤pH响应的聚合物胶束用于肿瘤药物靶向输送的研究进展[J].药学学报,2009,44(12):1328-1335.
[2] MURA S,NICOLAS J,COUVREUR P. Stimuli-responsive nanocarriers for drug delivery[J]. Nature Mater,2013,12(11):991-1003
[3] CHO K,WANG XU,NIIE S,et al. Therapeutic nanoparticles for drug delivery in cancer[J]. Clin Cancer Res,2008,14(5):1310-1316.
[4] NICOLAS J,MURA S,BRAMBILLA D,et al. Design,functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery[J]. Chem Soc Rev,2013,42(3):1147-1235.
[5] ZHANG L,XIA J,ZHAO Q,et al. Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs[J]. Small,2010,6(4):537-544.
[6] ARAP W,PASQUALINI R,RUOSLAHTI E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model[J]. Sci,1998,279(5349):377-380.
[7] DANHIER F,FERON O,PRAT V. To exploit the tumor microenvironment:passive and active tumor targeting of nanocarriers for anti-cancer drug delivery[J]. J Control Release,2010,148(2):135-146.
[8]王子琪,王狄狮,李馨儒,等.紫杉醇的pH敏感聚合物胶束的制备及其体外释放研究[J].中国新药杂志,2018,27(4):459-464.
[9] WANG T,D'SOUZA GM,BEDI D,et al. Enhanced binding and killing of target tumor cells by drug-loaded liposomes modified with tumor-specific phage fusion coat protein[J]. Nanomedicine,2010,5(4):563-574.
[10] HU C,WANG X,HUANG P,et al. A facile strategy to prepare an enzyme-responsive mussel mimetic coating for drug delivery based on mesoporous silica nanoparticles[J]. Langmuir,2017,33(22):5511-5518.
[11]金新天,刘刚,李君哲,等.透明质酸修饰的介孔二氧化硅包覆金纳米棒的制备及在肿瘤化疗-热疗联合治疗中的应用[J].高等学校化学学报,2016,37(2):224-231.
[12] CHEN WH,LUO GF,LEI Q,et al. Rational design of multifunctional magnetic mesoporous silica nanoparticle for tumor-targeted magnetic resonance imaging and precise therapy[J]. Biomaterials,2016,76(10):87-101.
[13] CHEN WH,LUO GF,QIU WX,et al. Mesoporous silica-based versatile theranostic nanoplatform constructed by layer-by-layer assembly for excellent photodynamic/chemo therapy[J]. Biomaterials,2017,117:54-65.
[14] MANCHUN S,DASS CR,SRIAMORNSAK P. Targeted therapy for cancer using pH-responsive nanocarrier systems[J]. Life Sci,2007,80(5):381-387.
[15] MURDZHEVA D,PETKOVA N,TODOROVA M,et al. Microwave-assisted synthesis of methyl esters of alginic acids as potential drug carrier[J]. J Pharmaceut Biomed,2016,8(10):1361-1368.
[16]周毅,李旭丰,谭璐,等.海藻酸栓塞微球可视化及作为药物载体研究进展[J].中国新药杂志,2017,26(9):1024-1028.
[17] MANCHUN S,DASS CR,SRIAMORNSAK P. Targeted therapy for cancer using pH-responsive nanocarrier systems[J]. Life Sci,2007,80(5):381-387.
[18] HU C,HUANG P,ZHENG Z,et al. A facile strategy to prepare an enzyme-responsive mussel mimetic coating for drug delivery based on mesoporous silica nanoparticles[J]. Langmuir,2017,33(22):5511-5518.
[19]许金霞,唐建斌,赵鲁杭,等.肿瘤pH响应的聚合物胶束用于肿瘤药物靶向输送的研究进展[J].药学学报,2009,44(12):1328-1335.